Salidroside Improves Chronic Stress Induced Depressive Symptoms Through Microglial Activation Suppression.

Yang Fan,Yajuan Bi,Haixia Chen

doi:10.3389/fphar.2021.635762

Abstract

Depression is a severe neurological disorder highly associated with chronic mental stress stimulation, which involves chronic inflammation and microglial activation in the central nervous system (CNS). Salidroside (SLDS) has been reported to exhibit anti-neuroinflammatory and protective properties on neurological diseases. However, the mechanism underlying the effect of SLDS on depressive symptoms has not been well elaborated. In the present study, the effects of SLDS on depressive behaviors and microglia activation in mice CNS were investigated. Behavioral tests, including Forced swimming test (FST), Open field test (OFT) and Morris water maze (MWM) revealed that SLDS treatment attenuated the depressive behaviors in stress mice. SLDS treatment significantly reduced the microglial immunoreactivity for both Iba-1 and CD68, characteristic of deleterious M1 phenotype in hippocampus of stress mice. Additionally, SLDS inhibited microglial activation involving the suppression of ERK1/2, P38 MAPK and p65 NF-κB activation and thus reduced the expression and release of neuroinflammatory cytokines in stress mice as well as in lipopolysaccharide (LPS)-induced primary microglia. Also, SLDS changed microglial morphology, attachment and reduced the phagocytic ability in LPS-induced primary microglia. The results demonstrated that SLDS treatment could improve the depressive symptoms caused by unpredictable chronic stress, indicating a potential therapeutic application of SLDS in depression treatment by interfering microglia-mediated neuroinflammation.

Highlights

Based on the statistical analysis from the World Health Organization, over 450 million people suffer from depression and it will rise to the top financial burden among all the diseases in 2030 (Ustun et al, 2004; Smith 2014; Kato and Kanba, 2015)
Our results showed that chronic stress increased the phosphorylation of ERK1/2, p38 MAPK, NF-κB p65 in the mice hippocampus area, which was prohibited in the SLDS treated group (Figures 2F–H). iNOS is an inducible nitric oxide synthase that is induced after brain injury and neuroinflammation
The results revealed that SLDS significantly attenuated activation of ERK1/ 2, p38 MAPK, NF-κB and expression level of iNOS in LPSstimulated primary microglia (Figures 3E–G), which were consistent with the results that were found in chronic stress exposed mice

Summary

Introduction

Based on the statistical analysis from the World Health Organization, over 450 million people suffer from depression and it will rise to the top financial burden among all the diseases in 2030 (Ustun et al, 2004; Smith 2014; Kato and Kanba, 2015). The pathogenesis of depression is still unclear, multiple studies suggested that chronic mental stress might be one of the critical pathogenic factors during depression formation and progression (Patriquin and Mathew 2017; da Estrela et al, 2020). Recent studies have shown that long-term stress impacts multiple aspects of biological systems, such as neuroendocrine, autonomic regulation, and behaviors (Sterlemann et al, 2008). This long-term stimulation eventually leads to a Salidroside Improves Depressive Symptoms failure in normal stress responses and brain inflammation, and causes mental disorders (Goshen et al, 2008; Patriquin and Mathew 2017)

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Conclusion